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Pharmacol Ther. 2019 Mar;195:54-84. doi: 10.1016/j.pharmthera.2018.10.004. Epub 2018 Oct 12.

Statins: Adverse reactions, oxidative stress and metabolic interactions.

Author information

1
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
2
College of Life Science, Yangtze University, Jingzhou, China; Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic.
3
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid 28040, Spain.
4
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
5
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid 28040, Spain. Electronic address: aanadon@ucm.es.
6
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid 28040, Spain; National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: wangxu@mail.hzau.edu.cn.

Abstract

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities. Widespread attention has been given to statin-induced oxidative stress, with and without the use of other drugs. Much of the information about the mechanism for this reduction comes from cell culture and in experimental animal studies. The primary focus of this article is to summarize the research progress associated with oxidative stress as a plausible mechanism for statin-induced toxicity, as well as its metabolic interactions. This review summarizes the research conducted over the past five years into the production of reactive oxygen species, oxidative stress as a result of statin treatments, and their correlation with statin-induced toxicity and metabolism. Statin-induced metabolism involves various CYP450 enzymes, which provide potential sites for statin-induced oxidative stress, and these metabolic factors are also reviewed. The therapeutics of a variety of compounds against statin-induced organ damage based on their anti-oxidative effects is also discussed to further understand the role of oxidative stress in statin-induced toxicity. This review sheds new light on the critical roles of oxidative stress in statin-induced toxicity and prevention of this oxidative damage, as well as on the contradictions and unknowns that still exist regarding statin toxicity and the cellular effects in terms of organ injury and cell signaling pathways.

KEYWORDS:

Metabolic interaction; Oxidative stress; Statins; Toxicology

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